title: miRNA expression is modulated over time after focal ischaemia: up-regulation of miR-347 promotes neuronal apoptosis.
abstract: Despite the large number of molecules reported as being over-expressed after ischaemia, little is known regarding their regulation. miRNAs are potent post-transcriptional regulators of gene expression, and reports have shown differentially miRNA expression in response to focal cerebral ischaemia. The present study analysed miRNA expression from acute to late phases of ischaemia to identify specific ischaemia-related miRNAs, elucidate their role, and identify potential targets involved in stroke pathophysiology. Of 112 miRNAs, 32 showed significant changes and different expression profiles. In addition to the previously reported differentially expressed miRNAs, new ischaemia-regulated miRNAs have been found, including miR-347. Forty-seven genes involved in brain functions or related to ischaemia are predicted to be potential targets of the differentially expressed miRNAs after middle cerebral artery occlusion. Analysis of four of these targets (Acsl4, Arf3, Btg2 and Dpysl5) showed them to be differentially regulated by ischaemia at the transcriptional or post-transcriptional level. Acsl4, Bnip3l and Phyhip, potential targets of miR-347, were up-regulated after miR-347 over-expression, inducing neuronal apoptotic death. Our findings suggest that miR-347 plays an important role in regulating neuronal cell death, identify Acsl4 as a new protein requiring study in ischaemia, and provide an important resource for future functional studies of miRNAs after ischaemia.
authors.affiliation: Grup de Recerca Cerebrovascular, Servei de Neurologia, Institut d'Investigació Biomèdica de Girona Dr Josep Trueta, Hospital Universitari de Girona, Spain.
authors.forename: Carme
authors.initials: C
authors.lastname: Gubern
authors.forename: Susanna
authors.initials: S
authors.lastname: Camós
authors.forename: Iván
authors.initials: I
authors.lastname: Ballesteros
authors.forename: Rocío
authors.initials: R
authors.lastname: Rodríguez
authors.forename: Víctor G
authors.initials: VG
authors.lastname: Romera
authors.forename: Roberto
authors.initials: R
authors.lastname: Cañadas
authors.forename: Ignacio
authors.initials: I
authors.lastname: Lizasoain
authors.forename: María A
authors.initials: MA
authors.lastname: Moro
authors.forename: Joaquín
authors.initials: J
authors.lastname: Serena
authors.forename: Judith
authors.initials: J
authors.lastname: Mallolas
authors.forename: Mar
authors.initials: M
authors.lastname: Castellanos
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D007511:Ischemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C521959:BTG2 protein, rat; D015415:Biomarkers; D017874:Immediate-Early Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C492129:Arf3 protein, rat; D020727:ADP-Ribosylation Factors; C500958:Acsl4 protein, rat; D003066:Coenzyme A Ligases
keywords: Acsl4; Arf3; MCAO; cerebral cortex; miR-347